Background: Helicobacter pylori, which is a causative agent of chronic gastritis, duodenal ulcer and gastric cancer, presently affects approximately one half of the world population. This study was conducted to assess the epidemiology and risk factors for acquisition of H. pylori among individuals with and without peptic ulcer symptoms in Owerri, Nigeria, in order to provide baseline data and create awareness for effective management and  prevention of infection caused by this pathogen. Methodology: A total of 384 participants, symptomatic and asymptomatic for peptic ulcer, were recruited from the three Local Government Areas (LGAs) of Owerri, Imo State, Nigeria. The symptomatic participants were randomly recruited among patients attending outpatient clinics with  symptoms of peptic ulcer disease at the Federal Medical Center Owerri, general hospitals and primary healthcare centers across Owerri LGAs, while  asymptomatic patients were recruited from the community. Information on socio-demographic characteristics of each participant and potential risk factors were collected with a pre-tested structured questionnaire. Blood samples were collected for detection of antibodies (IgG) using a one-step H.  pylori test device while faecal samples were collected for detection of occult blood (from peptic ulceration) using faecal occult blood (FOB) test.  Data were analyzed using SPSS version 25.0 and association of risk factors with H. pylori sero-prevalence was determined by the Chi-square or  Fisher Exact test (with Odds ratio). P value < 0.05 was considered statistically significant. Results: The sero-prevalence of H. pylori infection among the study participants was 72.4% (285/384) while the prevalence of ulcer by FOB test was  71.1% (273/384). A total of 78.4% (214/273) of those with ulcers were seropositive for H. pylori while 64.0% (71/111) of those without ulcers were  sero-positive for H. pylori (p=0.0045). Factors significantly associated with high sero-prevalence of H. pylori were age groups 41-50 (100%), 21-30  (78.4%) and 31-40 (67.6%) years (X2=66.964, p<0.0001), illiteracy (OR=6.888, p<0.0001), unemployment (OR=2.427, p<0.0001), low social class status  (X2=28.423, p=0.0003), drinking of unclean water (OR=5.702, p<0.0001), living in crowded rooms (OR=2.720, p<0.0001), eating food bought from  food vendors (OR=3.563, p<0.0001), family history of ulcer (OR=12.623, p<0.0001), habits of eating raw vegetables and unwashed fruits (OR=6.272,  p<0.0001), non-regular hand washing practices before meal (OR=2.666, p<0.0001) and presence of ulcer (OR=2.043, p=0.0045). However, smoking  (OR=0.7581, p=0.2449) and gender (OR=0.6538, p=0.0796) were not significantly associated with sero-prevalence of H. pylori. Conclusion: There is  need for comprehensive strategy including public health education campaign to create awareness on H. pylori, improve personal hygiene and environmental sanitation, provision of safe drinking water by the government to the populace, and discourage indiscriminate and open defecation.